Ethanol → (2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-{[5-(4-methoxybenzyloxy)-1-methyl-1H-pyrazole-3-carbonyl]amino}pentanoic Acid

참여 물질

역할	이름	HCID	투입량
반응물	Ethanol	HCID 702	—
반응물	Water	HCID 962	—
반응물	Lithium Hydroxide	HCID 3939	—
반응물	Dimethylformamide	HCID 6228	—
반응물	Diisopropylethylamine	HCID 81531	—
반응물	O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate	HCID 42624899	—
반응물	(2R,4R)-4-amino-5-(3'-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester	HCID 86682253	—
반응물	5-(4-Methoxybenzyloxy)-1-methyl-1H-pyrazole-3-carboxylic Acid	HCID 86705138	—
생성물	(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-{[5-(4-methoxybenzyloxy)-1-methyl-1H-pyrazole-3-carbonyl]amino}pentanoic Acid	HCID 86705139	70.5%

반응 단계

5-(4-Methoxy-benzyloxy)-1-methyl-1H-pyrazole-3-carboxylic acid (118.8 mg, 453 mol) was combined with HCTU (187.3 mg, 453 μmol) and DMF (2.0 mL, 25.9 mmol). The mixture was stirred at room temperature for 15 minutes. DIPEA (225 μL, 1.3 mmol) and (2R,4R)-4-amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester (150 mg, 430 μmol) were added and the mixture was stirred at room temperature for 15 minutes. The solvent was removed in vacuo. EtOH (1.5 mL, 25.9 mmol) was added, followed by a solution of 1 M LiOH in water (4.3 mL, 4.3 mmol). The mixture was stirred at room temperature for 1 hour. The solvent was removed in vacuo and the product was purified by reverse phase chromatography to yield the title compound (171 mg).

출처 및 근거

DOI	10.6084/m9.figshare.5104873.v1
특허 번호	US09108934B2
출처 데이터셋	uspto-grants-2015_08
ORD ID	ord-7ebbacd29781469a942d8344b2262580
출처 메모	uspto-grants-2015_08